Conventional wisdom has held for decades that free radicals cause aging, and that antioxidants, which squelch the reactivity of these highly reactive molecules, are a way to slow the process. But new work adds to a growing body of research that suggests the story is not so simple.
In the new study published in PLoS Biology, worms that made more free radicals, or were treated with a free-radical-producing herbicide, lived longer than normal worms.
What's more, when the longer-lived mutant worms were given antioxidants, the effects were reversed, and the worms had a conventional worm lifespan. The finding flies in the face of the idea that antioxidants battle the effects of aging.
According to study author Siegfried Hekimi of McGill University in Montreal and colleagues, what is emerging from this and other experiments is a view of free radicals - or, more precisely, reactive oxygen species - as a normal part of the body's stress response, with beneficial effects at certain levels.
"Maybe the reason why free radicals and ageing are correlated is because free radical production in the mitochondria (part of the cell) is a stress reaction to the damage of aging," says Hekimi. "The organism tries to counter with free radical production."
A little bit may be good
Hekimi and others point out that part of exercise's benefit may be because exercise causes mild increases in the levels of reactive oxygen species that are actually good for us.
The emerging view casts a pall on the idea of popping antioxidant pills in hopes of slowing the aging process or protecting against disease.
"When clinical trials have been done with antioxidants, they have not shown benefits," says Hekimi.
"If we're right that reactive oxygen species are fundamental to maintain normal fitness and also adaptation to stress, then you don't want to take too many antioxidants," says Navdeep Chandel of Northwestern Medical School in Chicago.
Indeed, Chandel suspects that the beneficial effects of limited alcohol consumption come not from antioxidants in red wine but from the mild oxidative stress the alcohol provides.
"Who am I to say if you should take antioxidants or not," he adds. "All I would say is there is no evidence that taking more antioxidants than you get through diet is needed."
Balancing free radicals effect
Free radicals do cause damage, says Hekimi, but at normal levels their beneficial effects are perhaps more important. If the stress of ageing or disease increases sufficiently, he says, the damage caused by the free radicals might overwhelm their positive effects.
"You cannot live without them, nor should you wish to, but they will probably help to kill you in the end," says Barry Halliwell of the National University of Singapore, of reactive oxygen species.
"Learning how to stop the latter whilst preserving the useful functions of reactive oxygen species should be a major research priority in the next few years."
Halliwell says evidence supports that reactive oxygen species probably contribute to the progression of cancer and neurodegenerative diseases, despite having beneficial effects at lower levels. They also probably cause skin wrinkling, he adds.
Hekimi hopes further experiments will determine exactly how reactive oxygen species increase lifespan in the worms.
He and his colleagues used the nematode worm Caenorhabditis elegans, an organism used widely in lab studies, but Hekimi believes the findings will translate into higher organisms like mice and humans, because these systems are so fundamental.
Halliwell noted, though, that C. elegans cannot be used to study the effect of free radicals on stem cells, which evidence suggests may be important. Also, the study only shows the effects of free radicals on longevity, and can say nothing about quality of life.